Project Summary Psychotic disorders are serious and debilitating mental illnesses that incur substantial suffering for patients and present major challenges to our health care system. Difficulties with emotion regulation (i.e., the ability to control the emotion response using strategies) significantly predict the development and maintenance of psychotic symptoms and poor community-based functional outcomes. Recent neuroimaging research indicates that hypofrontality may underlie these deficits. Unfortunately, there is no accepted technique for remediating these emotion regulation abnormalities in psychotic disorders. Recent advances from the field of cognitive neuroscience provide hope for a resolution to this critical unmet need in psychotic disorder therapeutics, demonstrating that brief computerized cognitive training interventions are capable of improving emotion regulation ability by targeting neural activation in the prefrontal cortex. The goal of the proposed project is to determine whether an emotional working memory (eWM) cognitive training program is effective for remediating emotion regulation abnormalities and associated clinical outcomes in people with psychotic disorders. In the R61 phase, outpatients with psychotic disorders will be randomly assigned to either an eWM (n = 20) or placebo (P: n = 20) cognitive training control intervention delivered via an app on a smartphone for 20 days. The primary aim of the R61 phase is to determine whether the eWM intervention successfully engages the target mechanism and enhances prefrontal activation on a non-trained emotion regulation transfer task beyond a pre-specified effect size criterion. Results of the R61 will also be used to determine the treatment modality (i.e., audio-only, visual-only, or combined audio-visual) and duration (10 vs. 20 days) that most effectively and efficiently improves the target. The goal of the R33 is to conduct an initial randomized controlled trial (RCT) of the optimal treatment identified in the R61. The R33 specific aims are to: 1) replicate and extend the R61 results supporting prefrontal target engagement in an adequately powered RCT (n = 80, 40 eWM, 40 P training); 2) determine if target engagement is associated with a proximal outcome of improved real-world emotion regulation ability (indexed via computational modeling of ecological momentary assessment data) and distal clinical outcomes of improved positive symptoms, negative symptoms, functional outcome, and neurocognition. If the R33 hypotheses are confirmed, results will inform the design of a later RCT for the early stages of psychosis, and to move toward a precision medicine approach that identifies which individuals are most likely to benefit from the intervention.